Role Of Glomerular Filtration Rate Research Articles

GFR decline predicts total mortality and mediates the effect of tryptophan metabolism on death risk in type 2 diabetes.

The independent role of glomerular filtration rate (GFR) decline in shaping the risk of mortality in people with type 2 diabetes has only been partially addressed. The objective of the study was twofold: i) to investigate the association between all-cause mortality and eGFR changes over time; ii) to understand whether renal dysfunction mediates the effect of tryptophan metabolism on death risk. Prospective study with an average follow-up of 14.8 years. Research Hospital. The aggregate Gargano Mortality Study included 962 patients with type 2 diabetes who had at least three eGFR recordings and at least 1.5 years of follow-up. This was an observational study, with no intervention. Rate of all-cause mortality. Age and sex adjusted annual incident rate of mortality was 2.75 events per 100 person-years. The median annual rate of decline of eGFR was 1.3 ml/min per 1.73 m2 per year (range -3.7; 7.8). The decline of kidney function was strongly and independently associated with the risk of death. Serum kynurenine-to-tryptophan ratio (KTR) was associated with both eGFR decline and all-cause mortality. Causal mediation analysis showed that 24.3% of the association between KTR and mortality was mediated by eGFR decline. In patients with type 2 diabetes, eGFR decline is independently associated with the risk of all-cause mortality and mediates a significant proportion of the association between tryptophan metabolism and death.

The role of glomerular filtration rate in AVF success: Should we intervene earlier?

End-stage kidney disease (ESKD) patients require life-sustaining kidney replacement therapies, with the natural arteriovenous fistula (AVF) being the preferred vascular access due to its low infection risk, high patency, and fewer complications. Factors like vessel diameter, gender, diabetes, age, and surgical technique influence AVF maturation. Our study focused on short-term AVF creation success, specifically examining estimated glomerular filtration rate (eGFR) levels using the CKD-EPI formula. Patients were categorized according to their eGFR levels to observe the effects of fistula timing and the severity of kidney disease. No significant demographic or outcome differences between eGFR groups have been observed except for gender. AVF maturation was notably associated with distal vein diameter (>2mm), while other factors did not significantly impact maturation rates. As a secondary outcome, it was concluded that the recording of patients' blood pressure values at preoperative and perioperative levels led to the conclusion that blood pressure levels may have an impact on fistula maturation. To ensure vascular access effectiveness, optimizing blood pressure, determining vein diameter, strategic AVF timing, and reducing catheter usage are crucial. Our study aimed to identify eGFR levels conducive to optimal AVF outcomes. Although significant results could not be obtained in this regard, it is considered worthwhile to re-examine the effect of blood pressure in secondary outcomes. Additionally, prospective studies may be appropriate for reevaluating the effect of GFR.

Acute Kidney Injury in Cardiac Surgery Patients: Role of Glomerular Filtration Rate and Fat-Free Mass.

Summary. Background.eGFR (estimated glomerular filtration rate) formulas may be inaccurate in overweight cardiac surgery patients, overestimating the kidney reserve. The aim of this study was to modify the eGFR formulas and to determine whether the modified eGFR is a more accurate predictor of acute kidney injury (AKI).Materials and methodsThe patients were assigned into 4 BMI groups as follows: normal weight (18.5– 25 kg/m2), pre-obesity (25–30 kg/m2), class I obese (30–35 kg/m2), class II and III obese (≥35 kg/m2). Cockcroft– Gault (CG) eGFR formula was modified by using the fat-free mass (FFM) derived from bioelectrical impedance. ROC-AUC curves were analyzed to identify the accuracy of the eGFR formulas (CG, CG modified with FFM, Mayo Clinic Quadratic equation, CKD-EPI, MDRD) to predict the AKI in each group. ResultsAlthough all of the used equations showed similar predictive power in the normal weight and overweight category, Mayo formula had the highest AUC in predicting the occurrence of AKI (ROC-AUC 0.717 and 0.624, p<0.05). However, in the group of patients with class I obesity, only the CG formula modified with a fat-free mass appeared to be predictive of postoperative AKI (ROC-AUC 0.631 p<0.05). None of the equations were accurate in the group of BMI (>35 kg/m2).ConclusionseGFR is a poor predictor of AKI, especially in the obese patients undergoing cardiac surgery. The only equation with a moderate predictive power for the class I obese patients was the CG formula modified with the fat-free mass.

Role of glomerular filtration rate-modifying drugs in the development of anticoagulant-related nephropathy.

IntroductionAnticoagulant‐related nephropathy (ARN), that was described in humans first as warfarin‐related nephropathy, is characterized by acute kidney injury and red blood cell (RBC) tubular casts in the kidney. 5/6 nephrectomy (5/7NE) rats treated with warfarin or dabigatran show changes in kidney function and morphology that are similar to human disease. The role of glomerular filtration rate (GFR) in the pathogenesis of ARN is not clear. The aim of these studies was to elucidate the role of GFR in the pathogenesis of dabigatran‐induced ARN in 5/6NE rats.Methods5/6NE rats were treated per os with 150 mg/kg/day dabigatran alone or with drugs that lower (enalapril, 1.5 mg/kg/day) or increase (albuterol, 4.0 mg/kg/day) GFR for 7 days. Changes in coagulation and kidney function were recorded daily. Kidney morphology was evaluated on day 7 after the treatment.ResultsDabigatran resulted in activated partial thromboplastin time increase that was not affected by GFR‐modifying drugs. Blood pressure was significantly lower in 5/6NE rats treated with enalapril and dabigatran as compared to dabigatran alone. The GFR was decreased by 35% in enalapril/dabigatran‐ and increased by 26% in albuterol/dabigatran‐treated animals. There were no changes in serum creatinine, hematuria or urinary kidney injury molecule (KIM‐1) levels when GFR‐modifying drugs were added to dabigatran. All dabigatran‐treated animals had RBC casts in the kidney regardless of the GFR modification.ConclusionsGFR does not play a significant role in the dabigatran‐induced acute kidney injury in 5/6 nephrectomy model in rats. Based in these data, modification of GFR in patients with ARN is not warranted.

Role of Glomerular Filtration Rate (GFR)-Modifying Drugs in Prevention of Anticoagulant-Related Nephropathy (ARN)

Role of Glomerular Filtration Rate (GFR)-Modifying Drugs in Prevention of Anticoagulant-Related Nephropathy (ARN)

Prevalence of chronic kidney disease after preeclampsia

BackgroundPreeclampsia (PE), an endothelial disease that affects kidney function during pregnancy, is correlated to an increased future risk of cardiovascular and chronic kidney disease. The Kidney Disease Improving Global Outcomes (KDIGO) 2012 guideline emphasizes the combined role of glomerular filtration rate (GFR) and albuminuria in determining the frequency of monitoring of kidney function.ObjectivesIn this study we evaluated the prevalence of CKD in women with a history of PE. We investigated how many seemingly healthy women required monitoring of kidney function according to the KDIGO guideline.MethodsWe included 775 primiparous women with a history of PE. They were at least 4 months postpartum, and had no pre-existing hypertension, diabetes or kidney disease. We estimated GFR by the CKD-Epidemiology equation and urinary albumin loss by albumin creatinine ratio in a 24-h urine collection.ResultsMost women, 669 (86.3 %), had a normal GFR and absent albuminuria. Based on the KDIGO guideline, 13.7 % would require at least yearly monitoring of kidney function. Only 1.4 % were classified to be at high risk for kidney function deterioration.ConclusionMonitoring of kidney function seems relevant for about one in seven women with a history of PE, mainly due to albuminuria. Albuminuria should be evaluated postpartum to identify those women that need further monitoring of kidney function.

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Objectives The KDIGO 2012 criteria emphasize the independent role of glomerular filtration rate (GFR) and albuminuria to assess the prognosis of chronic kidney disease (CKD), as both relate independently to all-cause mortality and cardiovascular morbidity/mortality. In this study we want to determine the prevalence of CKD in women with a recent history of preeclampsia. Methods We included 602 primiparous women with a history of preeclampsia. They were all at least 4 months postpartum and had no history of pre-existent hypertension, diabetes or kidney disease. We estimated GFR by the CKD-epi-equation, and quantified urinary protein loss (micro-albuminuria: >3.0 mg/mmol creatinine; macro-albuminuria: proteinuria >300 mg/24 h). We categorized women on the basis of the KDIGO 2012 criteria. Results Median time postpartum was 9 (6–18) months. Table 1 shows the different GFR and albuminuria categories. 419 (70%) women had a normal GFR and no albuminuria. Based on the KDIGO guideline, 77 (13%) women with a moderately increased risk would require yearly monitoring, in over 85% of the cases because of excessive urinary protein loss. Only 21 (3.5%) women were classified to be at high risk and would require referral to a nephrologist for twice yearly monitoring. Conclusions Follow-up of kidney function is relevant for about 16% of all women with a history of preeclampsia. Kidney function should be part of cardiovascular risk assessment after preeclampsia, with special emphasis to be directed on the postpartum disappearance of the preeclampsia-induced albuminuria. Disclosures J. Spaan: None. V. Lopez van Balen: None. L. Peeters: None. M. Spaanderman: None.

Prognostic value of chronic kidney disease in patients with coronary heart disease: Role of glomerular filtration rate estimating equations

Objective: Chronic kidney disease (CKD) increases risk of coronary heart disease (CHD), and different equations for estimating kidney function on CHD are available. Our aim was to describe the prognostic value of CKD as defined by various creatinine- (Cr-eGFR) and cystatin C-based (Cys-eGFR) estimating equations and their combinations on subsequent cardiovascular disease (CVD) events in patients with CHD. Material and Methods: All patients with CHD aged 30 to 70 years and participating in an in-hospital rehabilitation program between 01/1999 and 05/2000 were enrolled. In all patients, active follow-up was conducted 1, 3, 4.5 and 6 years after discharge from the rehabilitation center. CKD was defined as eGFR &lt;60 mL/min/1.73 m2 (CKD stage 3 to 5) estimated by three Cr-eGFR equations (CG/BSA, MDRD, Chronic Kidney Disease Epidemiology (CKD-EPIcrea) equation) and by two Cys-eGFR equations (Arnal-Dade equation, CKD-EPIcys) and a combination. The primary endpoint of our study were subsequent physician-reported CVD events. Results: 1050 patients with coronary heart disease aged 30 to 70 years at baseline were included in this prospective cohort study (follow-up response 87.1%). During follow-up (mean time 63.4 months) 118 patients (11.2%) experienced CVD events. CKD assessed by the CG/BSA, the MDRD, and CKD-EPIcrea equations showed no statistically significant association with subsequent CVD events after adjustment for multiple covariates (hazard ratio (HR) 1.45 [95% CI, 0.81–2.59], HR 1.47 [95% CI 0.84–2.60], and HR 1.31 [95% CI, 0.72–2.83) respectively). By contrast, the Cys-eGFR equations were much stronger associated with secondary CVD endpoints (Arnal-Dade: HR, 2.01 [95% CI, 1.34–3.04]; CKD-EPIcys HR, 2.22 [95% CI, 1.46–3.37]). The CKD-EPIcys also provided the highest Area Under Curve value. Conclusion: Our study shows that prevalent CKD is an independent risk factor for subsequent CVD in patients with prevalent CHD and implies that Cys-eGFR equations show a better clinical utility.

Role of Glomerular Filtration Rate in Controlling Blood Pressure Early in Diabetes

Perhaps the most obvious, and least contentious, examples of hypertension caused by the kidneys are renal artery stenosis and diabetic nephropathy, because there are readily identifiable, physical limitations in the ability of the kidneys to excrete sodium in each case. The former is characterized by a global restriction in renal perfusion, and the latter is characterized more specifically by glomerular injury and reduced glomerular filtration rate (GFR), but in each case there must be an increase in arterial pressure to maintain salt and water balance.1–3 Thus, in long-standing diabetes, types 1 and 2, a progressive decline in GFR is matched by a reciprocal increase in arterial pressure, which enables maintenance of sodium balance and body fluid volume homeostasis at the expense of deleterious adverse effects of chronic hypertension.4 In this framework, decreased GFR in diabetic nephropathy is responsible for imparting a chronic sodium-retaining influence on the kidneys, and hypertension is the counterbalancing natriuretic influence required to maintain sodium balance and sustain life. It, therefore, becomes curious that the early stages of diabetes are characterized by increased GFR and sodium balance, yet blood pressure is normal rather than low. For sodium balance to be maintained at normal blood pressure in the face of the chronic natriuretic influence of elevated GFR, there must be a concurrent sodium-retaining influence. If not, then the natriuretic effect of increased GFR would act unopposed and result in the maintenance of sodium balance at a lower blood pressure, similar to the effect of a diuretic. However, the presence of an underlying salt-retaining influence has been difficult to realize conceptually because of the increase in absolute sodium excretion in diabetes and because normal blood pressure typically does not spur research interest. This review focuses on how sodium balance is maintained at the onset of diabetes with …

Glomerular Filtration Rate and N-Terminal Pro-Brain Natriuretic Peptide as Predictors of Cardiovascular Mortality in Vascular Patients

The purpose of this work was to assess the prognostic role of glomerular filtration rate (GFR) and NT-terminal pro-B-type natriuretic peptide (NT-proBNP) for mortality end points in the vascular population. The GFR and NT-proBNP have been shown to predict mortality end points in free-living and limited vascular populations, independent of traditional risk factors. However, their prognostic power in an unrestricted vascular population is poorly understood. A total of 412 subjects from a vascular cohort with a history of either peripheral arterial disease (PAD) and/or other cardiovascular disease (CVD) were included in this prospective cohort analysis and followed for an average of 6.7 years. Outcome variables were all-cause mortality, ischemic heart disease (IHD) mortality, and any cardiovascular mortality. The prognostic roles of GFR and NT-proBNP levels were determined using multivariate survival analysis. Higher GFR (per 10 ml/min/1.73 m2) was significantly protective for all-cause mortality (hazard ratio [HR] 0.81, p < 0.001), IHD mortality (HR 0.82, p = 0.008), and CVD mortality (HR 0.84, p = 0.005). Conversely, NT-proBNP was not a significant predictor of any mortality end point. The GFR showed the strongest association in subjects with a history of other CVD. Although NT-proBNP did not demonstrate a significant prognostic role in any of the subgroups, the data were suggestive for patients with PAD alone. Glomerular filtration rate was a robust predictor of all-cause, IHD, and cardiovascular mortality in the vascular population, particularly in those with a history of other CVD, while NT-proBNP showed a suggestive association limited to the group with PAD only. These findings suggest that these markers must be selectively applied in the vascular population for greatest clinical utility.

Assessment of glomerular filtration rate in addition to albuminuria is important in managing type II diabetes

Although much emphasis has been placed on screening for albuminuria in type II diabetic patients, less attention has been focused on the role of glomerular filtration rate (GFR) in the assessment of risk. Herein, we examined the association between GFR and vascular complications in a consecutive cohort of 5174 type II diabetic patients between 1995 and 2000. Renal function was assessed by GFR (estimated by Modification of Diet in Renal Disease equation). The frequency of chronic kidney disease (CKD) as defined by GFR <60 ml/min/1.73 m(2), micro- and macrovascular complications, and their associations were analyzed. In this study cohort, 6% had serum creatinine > or =150 micromol/l and 15.8% had CKD. After adjustment for potential confounders, including urinary albumin excretion, odds ratios [95% confidence interval (CI)] across different stages of estimated GFR (> or =90, 60-89, 30-59, 15-29, <15 ml/min/1.73 m(2)) for macrovascular disease were 1.00, 1.42 [1.12-1.80], 1.80 [1.32-2.45], 2.74 [1.64-4.56], and 4.05 [1.77-9.26], respectively (P for trend <0.001); for retinopathy were 1.00, 1.23 [1.04-1.46], 1.80 [1.40-2.30], 2.05 [1.25-3.37], and 4.12 [1.56-10.90], respectively (P for trend <0.001); for sensory neuropathy were 1.00, 1.53[1.27-1.85], 2.09 [1.58-2.76], 4.32 [2.41-7.77], and 3.16 [1.25-8.02], respectively (P for trend <0.001); and for microalbumuria (with GFR <15 ml/min/1.73 m(2) excluded from the analysis) were 1.00, 1.51 [1.30-1.75], 5.80 [4.52-7.44], and 52.5 [16.4-168.2] respectively (P for trend <0.001). Measurement of serum creatinine alone without GFR may underestimate renal impairment in type II diabetic patients. Decreasing GFR was significantly associated with increasing frequency of micro- and macrovascular complications.

Role of Glomerular Filtration Rate in the Impaired Sodium and Water Excretion of Patients With the Nephrotic Syndrome

Hemodynamic and hormonal factors were monitored in nine patients with nephrotic syndrome who were evaluated relative to their capacity to excrete a 20-mL/kg water load (normal greater than 80%). In five "nonexcretor" patients (37% of water load excreted in five hours), as compared to four normal excretors (105% of water load excreted in five hours; P less than .01 v nonexcretors), neither BP (131/88 v 119/79 mm Hg), pulse (74 v 77 beats/min), cardiac index (3.7 v 3.1 L/min/m2), pulmonary wedge pressure (9.3 v 7.3 mm Hg), systemic vascular resistance (1537 v 1254 dynes-sec-cm-5), nor plasma volume (41.3 v 40.1 mL/kg) were different. Similarly, plasma renin activity (2.6 v 3.7 ng/mL/h), plasma aldosterone (12 v 10.9 ng/dL), and plasma norepinephrine (403 v 312 pg/mL) were not different between nonexcretor v excretor patients with nephrotic syndrome. Plasma vasopressin concentrations were also similar both before (3.1 +/- 0.8 v 2.4 +/- 1.2 pg/mL) and during the water load (0.9 +/- 0.3 v 1.0 +/- 0.4 pg/mL). Inulin clearances, however, were lower in the nonexcretor v the excretor nephrotic patients (37 v 78 mL/min/1.73 m2; P less than .02) and correlated with water excretion (r = .68; P less than .05). Head-out water immersion increased sodium (40 to 110 microEq/min; P less than .01) and water excretion (37% to 82%; P less than .025) in the nonexcretors; the improvement correlated with the increase in inulin clearance during immersion (r = .70; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dietary protein restriction and glucocorticoid administration on urea excretion in rats

Rats were sampled for clearance studies under anesthesia after 0, 2, 4, 7 and 14 days of dietary protein restriction. Mean fractional urea excretion decreased between day 2 and day 7 of protein restriction after a two-day lag in response. Seven-day administration of dexamethasone in protein-restricted rats caused a significant increase in mean fractional urea excretion. Adrenalectomized rats fed a normal diet had fractional urea excretion values resembling those in protein-restricted rats. Chronic administration of dexamethasone in adrenalectomized rats caused a consistent increase in fractional urea excretion. Fractional urea excretion values were no lower in protein-restricted adrenalectomized rats fed a normal diet. The mean plasma corticosterone concentration (measured 6 to 8 PM) was decreased in rats fed a low protein diet relative to rats fed a high protein diet. The results suggest that glucocorticoids may play a role in the tubular regulation of urea excretion either by a direct effect on the renal tubule or through some intermediate factor. A mediating role of glomerular filtration rate in glucocorticoid-induced changes of fractional urea excretion could not be ruled out, however.

Diurnal variations of lithium clearance in the rat.

The rate of urinary excretion of lithium was studied in the morning (light) and in the evening (dark) in rats given lithium in the food or by intraperitoneal injection. Lithium clearance was highest during the night. The diurnal variation of lithium clearance was proportional to the diurnal rhythm of glomerular filtration rate. The role of glomerular filtration rate in the diurnal variation of lithium clearance is discussed.

Sodium conservation and control of glomerular filtration rate

Experiments on dogs were designed to study the role of glomerular filtration rate (creatinine clearance, CCr) in sodium homeostasis. Dogs were studied on a normal Na intake (salted) and after Na had been removed from the diet (unsalted). In both instances CCr was estimated before and after rapid expansion of extracellular fluid volume (ECF) with glucose, mannitol, or NaCl solutions. Before expansion of ECF, CCr showed no consistent change relating to Na-deficiency as such. Following expansion of ECF, CCr increased in dogs with normal intake of Na and decreased (or increased less) in nine out of ten comparisons in dogs with no Na in the diet. The percentage change in CCr elicited by ECF expansion correlated positively with change in plasma Na concentration and inversely with change in plasma potassium concentration, except following NaCl solution infusion or the inclusion of K in glucose infusions. Decreased CCr following ECF expansion in dogs with no Na in the diet was tentatively ascribed to intrarenally evoked vasoconstriction consequent to the loss of intracellular K from some undefined site.